New potent anthracyclines, barminomycins I and II.
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Biomedical subjects
Publications and source records attributed to T Takeuchi.
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Terpentecin at a concentration of 0.78 microgram/ml decreased the number of viable cells of Escherichia coli NIHJ to less than one thousandth the starting number in an hour when added to an exponentially growing culture in a nutrient broth. During this time, the turbidity of the cell suspension kept increasing as fast as the control. Microscopic inspection of the cells exposed to terpentecin under these conditions revealed that the cells were elongated. Terpentecin at a concentration of 6.25 micrograms/ml inhibited incorporation of [14C]thymidine into the acid-insoluble material of cells of E. coli NIHJ by 70% in 30 minutes in contrast to little or no inhibition of the incorporation of [14C]uridine or [14C]leucine. Under similar conditions, terpentecin did not inhibit either membrane transport (uptake) of [14C]thymidine into the cells or the metabolic conversion of the precursor into various cellular acid-soluble components. Terpentecin at a higher concentration (70 micrograms/ml) inhibited by 40% in 30 minutes the incorporation of [methyl-3H]thymidine triphosphate into the DNA fraction of toluene-treated cells of E. coli JE6296 (pol A-). Terpentecin showed stronger antibacterial activities against Bacillus subtilis M45T (rec-) and E. coli BE1121 (rec A-) than against their corresponding wild type strains. However, terpentecin showed no mutagenicity by the Ames test with Salmonella typhimurium strains TA100, TA98, TA92, TA1538, TA1537 and TA1535, and with E. coli WP2 (uvr A). Terpentecin at a lower concentration (0.07 micrograms/ml) inhibited growth in vitro of mouse leukemia L1210 cells by 50%. With the mammalian cells again the incorporation of [14C]thymidine into the acid-insoluble cell material was inhibited more strongly than incorporation of [14C]uridine and [14C]leucine. There was no sign of mutagenicity by the micronucleus test using mice.
DNA binding characteristics of ditrisarubicin B were studied by the fluorescence titration technique. Ditrisarubicin B bound to calf thymus DNA with an affinity higher than any we have ever seen among anthracyclines. The apparent association constant (Kapp) of ditrisarubicin B was 2.36 X 10(8) M-1, which is 22.7 times larger than that of doxorubicin. The apparent number of binding sites (napp) of ditrisarubicin B per nucleotide of DNA was 0.164, and this value is identical with that of doxorubicin. Betaclamycin A, which has a trisaccharide chain at C-7 but no carbohydrate at C-10 in the aglycone, interacted with DNA to give a Kapp of 5.92 X 10(6) M-1 and napp of 0.178. These results suggest to us that the high affinity of ditrisarubicin B for DNA is caused by the existence of a glycosidic chain at C-10.
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A case of non-specific granulomatous prostatitis is presented. A 61-year-old male consulted a doctor with the chief complaint of dysuria. For suspicion of prostate cancer, he was referred to our hospital. A digital examination showed stony hard prostate gland which was asymmetrically enlarged to hen's egg size with an irregular surface. Since biopsy specimen from the prostate showed eosinophilic granulation without fibrinoid necrosis, the case was diagnosed as simple nonspecific granulomatous prostatitis. After oral administration of chlormadinone acetate (CMA), he showed a remarkable increase in urinary stream. The findings of urethrogram and prostatic sonogram demonstrated dramatic improvement. He has remained asymptomatic for 29 months without any further treatment. Therefore, CMA could be effective against granulomatous prostatitis.
A semi-synthetic bleomycin analogue and its DNA binding moiety, an alkylamino-2-methoxy-6-chloroacridine, have been found to inhibit human immunodeficiency virus-associated reverse transcriptase. The authors have synthesized various new alkylaminoacridine derivatives. Alkylaminoacridines with basic functional groups showed the enzyme inhibitory activity with less cytotoxicity.
A 52-year-old, healthy looking woman was referred for further evaluation of left renal mass, She had had a history of hematuria for ten years. Admission laboratory studies were within normal limits except for slight elevation of white blood cell count, c-reactive protein, blood sedimentation rate and immunosuppressive acidic protein. Retrograde pyelography demonstrated a large mass with ringed calcification in the middle lobe of the left kidney. The multiloculated mass was also confirmed by computed tomography and ultrasonography. Selective left renal arteriography showed stretched arteries and irregularity and tortuosity of the smaller vessels. Under a presumptive diagnosis of multilocular cystic nephroma or renal cell carcinoma, left radical nephrectomy was performed. In surgical specimen, many lobules were filled with serous fluid and clotted blood. Microscopic examination revealed that the lining of the cyst wall consisted of renal cell carcinoma cell. At present, 5 months after the operation, she is well without any signs or symptoms of recurrence.
The clinical efficacy and safety of urapidil, used alone or in conjunction with beta-blockers, were evaluated in 14 patients with phaeochromocytoma. Following a 1-week placebo run-in period, the patients were treated with sustained-release capsules of urapidil, initially 30 mg twice a day, followed by dose adjustment within 30-270 mg (mean +/- s.d. 144 +/- 73) per day for 7-29 days (21 +/- 8 days). In six patients, beta-blockers were added to control associated tachycardia. Blood pressure and pulse rate were successfully controlled in 11/14 patients (78.6%) during the therapy. Both the frequency and the severity of hypertensive paroxysms were clearly reduced in 7/8 patients, who showed frequent paroxysms of hypertension during placebo treatment. A variety of subjective symptoms observed in 13 patients during placebo treatment improved during drug therapy in nine patients (69.2%). Side effects occurred in five patients but were minor and well tolerated except in one patient, who was withdrawn from urapidil monotherapy due to facial oedema and finger stiffness which persisted even after reducing the daily dose from 306 to 270 mg. Overall, in terms of antihypertensive effectiveness, improvement in subjective symptoms and the safety profile, urapidil was considered very useful in four patients (28.6%), useful in six (42.9%), slightly useful in three and useless in one. Urapidil therefore appears to be a worthwhile agent in the treatment of patients with phaeochromocytoma.
Techniques of a micro enzyme-linked immunosorbent assay (ELISA) used for the serodiagnosis of schistosomiasis were applied to amebic infection. Test sera were divided primary on the basis of serologic diagnosis and stool examination as follows; (I) gel diffusion precipitin test (GDP) positive and stool examination positive: 9 specimens, (II) GDP positive and stool examination negative: 29 specimens, (III) GDP negative and stool examination positive: 32 specimens. Virtually all of the individuals belonging to (III) were asymptomatic, while more than 75% of (I) and (II) were symptomatic. The upper limit of 99% critical range was calculated from the data of 70 serum specimens from healthy adult Japanese and was employed as the cut-off value. All of the specimens of (I) and (II) were judged positive by ELISA, generally with a much higher absorbance than the cut-off value; whereas, approximately 80% of (III) were judged positive. The average absorbance of (III) was lower than that of (I) and (II). These findings suggest that the ELISA is well in accord with GDP qualitatively as far as GDP-positive individuals are concerned, and that even asymptomatic cyst carriers with negative serology by GDP may often be producing anti-amebic antibodies, although the titers are low.
A case of pure, primary testicular carcinoid tumor in a 27-seven-year-old male is reported. The patient presented with a painless enlargement of the right testis but the serum markers for testicular cancer, including alpha-fetoprotein, beta-human chorionic gonadotropin and lactate dehydrogenase, were not elevated. Right orchiectomy was performed. Histologically, the tumor showed a typical appearance of carcinoid tumor. Further examinations such as barium studies, computed tomographic scan and Ga scintigraphy, showed no other lesions, and he received an adjuvant chemotherapy of cyclophosphamide, 5-fluorouracil and adriamycin. He is well and free from symptoms 17 months after surgery.
It was previously shown that autoregressive modeling can be used for feedback analysis in the body. We used this method to investigate the dynamic changes in and around the renin-angiotensin system in vivo induced by angiotensin-converting enzyme (ACE) inhibition. Long-term studies were performed on rabbits, which were given a daily injection of one of the following ACE inhibitors: captopril, foroxymithine, or histargin. For comparison, other rabbits received injections of saline or the renin inhibitor pepstatin. Autoregressive coefficients were computed from the raw data thus observed and were used to simulate the impulse-response function proper to each animal. The response of each animal estimated in this way exposed the effects of ACE inhibitors in vivo which were obscured by the feedback regulation of the renin-angiotensin system. Also, it was suggested that histargin has a peculiar action, blocking the negative feedback that would be elicited by the usual ACE inhibition. Feedback analysis seems to be essential to elucidate the in vivo effects of enzyme inhibitors.
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We report a case of pure choriocarcinoma of the left testis with multiple pulmonary and cerebellar metastases. A 25-year-old male was referred to our clinic because of painless swelling of the left scrotal content and multiple nodules shown in the chest X-ray. At hospitalization, the examination also revealed cerebellar metastasis. With left high orchiectomy, the lesion was confirmed to be pure choriocarcinoma. In spite of several treatments including surgical removal of metastatic brain tumor and combination chemotherapy, he died on the 79th hospital day. Pure choriocarcinoma of the testis is an uncommon disease. Only 46 cases have been reported in the literature before 1987.
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